1. Synthesis and biological evaluation of 1-(4′-Indolyl and 6′-Quinolinyl) indoles as a new class of potent anticancer agents
- Author
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Lai, Mei-Jung, Chang, Jang-Yang, Lee, Hsueh-Yun, Kuo, Ching-Chuan, Lin, Mei-Hsiang, Hsieh, Hsing-Pang, Chang, Chi-Yen, Wu, Jian-Sung, Wu, Su-Ying, Shey, Kuang-Shing, and Liou, Jing-Ping
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ORGANIC synthesis , *INDOLE , *DRUG synergism , *ANTINEOPLASTIC agents , *HETEROCYCLIC compounds , *CANCER cell proliferation , *BINDING sites , *DRUG resistance in cancer cells - Abstract
Abstract: A novel series of the biheterocycles-based compounds with core structure distinguished from combretastatin A-4 (1) and colchicine (5) have been synthesized and evaluated as potent anti-mitotic agents. Compound 1-(4′-Indolyl and 6′-quinolinyl)-4,5,6-trimethoxyindoles 13 and 19 showed substantial anti-proliferative activity against various human cancer cell lines, regardless to the tissue origin and the expression of multiple-drug resistance MDR1, with a mean IC50 value of 38 and 24 nM respectively. Compound 13 (IC50 = 1.7 μM) also exhibited similar anti-tubulin activities to 1 (IC50 = 1.8 μM) and displayed strong binding property to the colchicine binding site on the microtubules. Computational modeling analysis revealed that the binding mechanism of compound 13 is similar to that of CA4. [Copyright &y& Elsevier]
- Published
- 2011
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